SURVEY OF BIOCHEMISTRY Enzyme Kinetics and Inhibition

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SURVEY OF BIOCHEMISTRYEnzyme Kinetics and
Inhibition
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Rates of Chemical Reactions
Enzyme kinetics is the study of rates of
reactions catalyzedby enyzmes.
The rxn rate (velocity, v) can be described in
several ways 1 disappearance of reactant,
A 2 appearance of product, P These eqns
relate velocity to concentration of reactants and
products.
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Rate Laws
Enzyme kinetics is the study of rates of
reactions catalyzedby enyzmes.
A rate law is an equation describing the velocity
of achemical reaction. Differential Rate
Laws Integrated Rate Laws
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Differential Rate Laws

• Differential rate laws correspond to order of the
  reaction.

Order of Reaction Rate Law 0 v k 1 v
k A 2 v k A2 or kB2 or v k
A x B
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Integrated Rate LawsFirst Order

• Integrated rate laws express the rxn velocity in
  terms of time.

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Integrated Rate LawsFirst Order
At
Integrate onboth sidesof eqn
dA

- k dt
A0
(ln At constant) - (ln A0 constant)
- kt
ln At - ln A0 - kt
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Integrated Rate LawsFirst Order
ln At - ln A0 - kt
ln A ln A0 - kt
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Integrated Rate LawOther Versions of First Order
ln At - ln A0 - kt
first order rxn
Rearranging
Take exponentof both sides
e -kt
first order rxn
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Integrated Rate Law Second Order

• How does the integrated rate law change if the
  order of the reaction is second order?

Show result on board
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Michaelis-Menten Equation
Many enzymes obey Michaelis-Menten kinetics
behavior
Rate limiting step
Problem ES is difficult to measure!What can
we do?
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Michaelis-Menten Equation
Recall

• Assume equilibrium is maintained in 1st step
• Assume steady state

k1 E S - k-1 ES - k2 ES 0
Formation of ES
Depletion of ES
See notes on board
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Michaelis-Menten Kinetics
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Lineweaver-Burk Plot
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Enzyme Inhibition

• What is an inhibitor?
• Modes of Inhibition
• Competitivebinds to same site in E as S
• Uncompetitive
• Noncompetitive
• Mixed

bind to different site in E than S
Note Text does not distinguish non and mixed
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Competitive Inhibition

• Competitive inhibitors bind to the same site on E
  as S

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Competitive Inhibition
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Competitive Inhibition
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Uncompetitive Inhibition
Uncompetitive inhibitors bind directly to the ES
complex but not to the free enzyme
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Uncompetitive Inhibition
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Mixed Inhibition
Mixed inhibitors can bind to E or ES complexS
cannot bind if I is already bound!
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Mixed Inhibition
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Noncompetitive Inhibition
Noncompetitive inhibitors can bind to E or ES
complexS can bind even if I is already bound!
I
See board for plot
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Updates and Reminders

• Exam 2 in two weeks (June 26)
• Chapter 7 Protein Function
• Chapter 11 Enzyme Catalysis
• Chapter 12 Kinetics Inhibition
• Chapter 8 Carbohydrates
• Chapter 14 Introduction to Metabolism
• Suggested HW problems online this weekend
• Resources What You Should Know more coming soon